Altogether, these results indicate that (1) AKT3 is the main driver for microcephaly in the 1q43q44 region; (2) ZBTB18 haploinsufficiency may independently lead to microcephaly with a lower penetrance; and (3) co-deletion of AKT3 and ZBTB18, which are neighboring genes spaced from only ~200 Kb, may have an addictive effect, resulting in constant microcephaly. Here, AKT3 is linked to microcephaly.